Pharmacokinetics Of Tet In The Rabbit Eyes

Objective:To investigate pharmacokinetics of Tet eye drops by high-pressure liquid chromatography(HPLC).And to provide basis to prevent Haze after refractive operation in clinic.Methods:Eighteen New Zealand rabbits were divided into nine groups in random.There were two animals in each group.one 50ul drop was instilled in the eyes of rabbits in each group.Lacrimal fluid,Cornea,Aqueous humor,Iris-ciliary,Lens,Vitreous were obtained at 5,15,30,60,90,120,150, 180,240min after single topical administration.At each time point,two rabbits were killed.The drug concentrations were assayed by HPLC.Methanol-acetonitrile-distilled water(80:10:10) was used as mobile file. Flow rate was 0.8ml/min. The ultraviolet detector was set at 242nm wave-length. The column temperature was 30.The concentration was calculated by peak area.At last,to get pharmacokinetic parameters of Tet in rabbit eyes by 3p87. Results:Under this experimental conditions,the peak of Tet was well separated with the peak of globe and the retention time was about 7.5min.The calibration curve of Tet in rabbit eye had a good relationship between the concentration and peak area(r=0.9986).The precision was well. The intra-day and inter-day precision were both below 5%.The absolute recovery in all eye tissues were over 80%,and the relative recovery was about 95%.The stability of Tet at room temperature and after freeze thawing were below 15% in all eye tissues. The concentrations of Tet in Lacrimal fluid were quiukly cut down after single topical administration. The half life time was 38.316min.The elimination rate constant was 0.018/min.In intraocular tissues,the concentrations of Tet in cornea were highest, which was (18.77±2.11)μg/g after 5min and was (3.30±0.16)μg/g after 240min.Its half life time and elimination rate constant were 115.140min and 0.060/min respectively. The AUC in cornea which was 2336.294(μg/g)*min was the largest one in intraocular tissues.It explained that the drug had cumulated in the cornea after single topical administration.Conclusion:1,The concentration-time processes were found to fit extravascular does single compartment model after single topical administration.2,The concentrations of Tet in cornea were the highest of that in intraocular tissues after single topical administration, which can help Tet to prevent Haze in clinc.3,The pharmacokinetic parameters of Tet in rabbit eyes can provide experiment basis for its concrete medication scheme.